EP3217967B1 - System und verfahren zur verhinderung von alopezie - Google Patents

System und verfahren zur verhinderung von alopezie Download PDF

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Publication number
EP3217967B1
EP3217967B1 EP15858397.1A EP15858397A EP3217967B1 EP 3217967 B1 EP3217967 B1 EP 3217967B1 EP 15858397 A EP15858397 A EP 15858397A EP 3217967 B1 EP3217967 B1 EP 3217967B1
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weight
hair
synephrine
alpha
adrenergic receptor
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French (fr)
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EP3217967A4 (de
EP3217967A1 (de
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Ofer A. Goren
John Mccoy
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Follea International
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Follea International
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention is directed to methods for treating, reducing or preventing alopecia and other hair loss disorders caused by mechanical pulling of the hair, including but not necessarily limited to traction alopecia, and compositions, devices and kits useful in such methods.
  • Traction alopecia results from the chronic application of tensile force to scalp hair (1).
  • the condition was described as early as 1907 in subjects from Greenland who had developed hair loss due to prolonged wearing of tight ponytails (2).
  • traction alopecia has been related to specific hairstyles that cause increased tension on the scalp (e.g., ponytails, Afro-Caribbean hair styles with tight braiding or the tightly wound turbans of Sikh men). It has also been seen in female ballerinas. It is also seen in cultural traditions where the hair is voluntarily not cut in religious obeisance, which causes progressively increasing weight of the hair itself.
  • Traction alopecia is mechanical in etiology, rather than androgenic. Management includes cessation of the chronic traction. However, this is unacceptable to people who favor the specific hairstyles and styling techniques that give rise to the condition.
  • Traction alopecia is a substantial risk in hair extensions and weaves, which can be worn either to conceal hair loss, or purely for cosmetic purposes.
  • the latter involves creating a braid around the head below the existing hairline, to which an extended-wear hairpiece, or wig, is attached. Because the hair of the braid is still growing, it requires frequent maintenance, which involves the hairpiece being removed, the natural hair braided again, and the piece snugly reattached. The tight braiding and snug hairpiece cause tension on the hair that is already at risk for falling out.
  • Traction alopecia is one of the most common causes of hair loss in African American women.
  • Traction alopecia includes hair loss or shedding due to increased traumatic force on hair follicles caused by hairstyle or mechanical hair procedures such as blow drying, flat ironing, hair curling and chronic brushing. Traction alopecia can also develop in patients constantly pulling their hair such as in trichotillomania.
  • traction alopecia affected areas depend on the etiology of the disorder, but usually hair loss is localized on frontal and temporal scalp. According to population studies in African women, prevalence of traction alopecia varies from 17.1% in young women (6-21 years) to 31.7% in older women (18-86 years). Clinical features of traction alopecia include itching of the scalp, perifollicular erythema, scaling, folliculitis, and pustules, but it can also present as slow onset of hair loss without other symptoms. Primarily, traction alopecia is considered noncicatricial, yet excessive tension can lead to permanent alopecia, due to physical damage of hair follicles. Prolonged force on hair follicles may lead to inflammatory changes in immune cell infiltrate and fibrosis can result. Therefore, it is important to recognize the condition early, while it is still reversible.
  • compositions and methods are disclosed herein for the treatment and prevention of hair loss disorders caused at least in part by repeated application of tensile force to hair, including, without limitation, traction alopecia.
  • hair loss disorders caused at least in part by repeated application of tensile force to hair, including, without limitation, traction alopecia.
  • Such disorders may be treated or prevented by the application to the hair follicle or scalp of a compound or agent that induces contraction of the arrector pili (AP) muscle, such as, without limitation, alpha 1 adrenergic receptor agonists (A1AR agonists).
  • AP arrector pili
  • A1AR agonists alpha 1 adrenergic receptor agonists
  • Each hair follicle in the scalp contains an arrector pili muscle that, when contracted, erects the hair.
  • the smooth muscle in the arrector pili expresses ⁇ 1 adrenergic receptors ("A1AR").
  • A1AR ⁇ 1 adrenergic receptors
  • Disclosed herein are methods for the treatment and prevention of disorders associated with mechanical stress or pulling on the hair comprising topical administration to the scalp or hair follicle of a composition comprising one or more A1AR agonists. As shown herein, such agonists protect against hair loss or shedding as shown by an increase in epilation force needed to remove a hair and reduction in the number of hairs removed after brushing.
  • the compounds and agents used in the present invention stimulate contraction of the AP muscle and thereby reduce hair loss by increasing the force required to remove the hair.
  • A1AR agonists to promote the pilomotor effect is described in U.S. 4,853,216 , which is incorporated herein by reference in its entirety. There, the A1AR agonists were recognized as useful for causing hairs to stand up to facilitate closer shaving or to potentiate the effect of depilatories. That is, A1AR agonists were described there as agents that facilitate hair removal, as opposed to prevent hair loss.
  • A1AR agonists as agents useful for treating and preventing the disorders described herein relating to hair loss
  • any agent that stimulates contraction of smooth muscle, and particularly the AP muscle can be useful in the compositions and methods described herein. That is, unless specifically indicated otherwise, disclosure relating to uses or formulations of A1AR agonists should be considered to refer as well to other agents that stimulate AP muscle contraction.
  • traction alopecia means a form of alopecia (hair loss or hair shedding) associated with mechanical forces that pull the hair such as hair brushing hair combing, flat ironing, wearing of extensions, hair braiding, and ponytail style hair.
  • traction alopecia although chronic traction on the hair can lead to traction alopecia, the mechanical forces that pull the hair do not necessarily need to be chronic to lead to hair loss or excessive shedding.
  • the term "pilomotor effective” refers to an agent or treatment that stimulates contraction of the arrector pili muscle associated with a hair follicle.
  • a "pilomotor effective amount" of an agent or treatment is an amount sufficient to stimulate contraction of the arrector pili muscle.
  • alpha 1 adrenergic receptor agonist refers to a ligand that binds the alpha 1 adrenergic receptor on smooth muscle cells and activates smooth muscle contraction.
  • the terms “prevent” or “prevention” and other derivatives of the words when used in reference to alopecia, e.g., traction alopecia, refer to a reduced likelihood of alopecia in an individual receiving a given treatment relative to that of a similar individual at risk for alopecia but not receiving that treatment.
  • the terms “prevent” and “prevention” encompass a treatment that results in a lesser degree of alopecia, e.g., traction alopecia, than would be otherwise expected for a given individual.
  • Efficacy for prevention of alopecia can be established through controlled studies, e.g., in which a subject is administered a treatment (e.g., a topical treatment) at one site likely to experience or exhibit alopecia (e.g., for traction alopecia, a site at which hair is pulled for an extended period of time) but not at another site subjected to the same conditions.
  • a treatment e.g., a topical treatment
  • alopecia e.g., for traction alopecia, a site at which hair is pulled for an extended period of time
  • the site treated with the topical treatment undergoes less hair loss over time relative to the untreated site, e.g., at least 5% less, at least 10% less, at least 15% less, at least 20% less, at least 25% less, at least 30% less, at least 35% less, at least 40% less, at least 45% less, at least 50% less or beyond, the treatment is effective for the prevention of alopecia, e.g., traction alopecia.
  • alopecia e.g., traction alopecia.
  • Efficacy for the prevention of other forms of alopecia can be established in a similar manner, e.g., by treating one area affected by or likely to be affected by such alopecia, but not another, substantially similar area (i.e., subject to the same conditions causing alopecia or a likelihood of alopecia) and comparing hair loss or retention in the two areas.
  • the terms “treat,” “treatment,” or “treating” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a disease or condition, e.g., traction alopecia or other form of alopecia.
  • the term “treating” includes reducing or alleviating at least one adverse effect or symptom of a disease or condition, e.g., traction alopecia or other form of alopecia.
  • Treatment is generally “effective” if one or more symptoms are reduced. Alternatively, treatment is “effective” if the progression of a disease is reduced or halted.
  • treatment includes not just the improvement of symptoms, but also a cessation of, or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment.
  • Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), and/or decreased mortality.
  • treatment is considered effective if the extent or amount of hair loss is reduced, or the progression of hair loss is slowed or halted.
  • treatment also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).
  • the term “epilatory” relates to the removal of hair.
  • the term “increasing epilatory force” refers to any treatment that increases the physical force required to remove a hair.
  • the increase in force can be viewed as at least a partial balancing of a traction force by the force exerted by the arrector pili muscle - the vector direction of the arrector pili muscle's force of contraction need not necessarily be directly opposed to a traction force on the hair shaft to increase the epilatory force required to remove the hair, but the net effect is that the muscle provides at least a partial counter-acting force to the traction force, whether it directly pulls back on the hair or simply holds the hair or hair follicle more tightly in place.
  • An increase in epilatory force can be measured in several ways, including empirically, through a reduction in traction alopecia (e.g., 10% or less reduction in hair loss) despite continued or ongoing traction, or through measurement of actual force exerted on the hair follicle, e.g., with a myograph, trichotilometer, or a device used to measure tensile forces.
  • compositions, methods, etc. refers to component(s) or method steps that are present in the method or composition, yet allows for the composition, method, etc. to also include unspecified elements.
  • compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.
  • the term “consisting essentially of” refers to those elements required for a given embodiment. The term permits the presence of elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment.
  • the technology described herein relates to the prevention of traction alopecia.
  • One preventive approach currently available for traction alopecia is to remove, limit or avoid the application of a traction force to the hair.
  • hairstyles or other factors that pull on the hair e.g., tight fitting helmets
  • hairstyles or other factors that pull on the hair should normally be avoided to prevent traction alopecia.
  • the approaches set out herein such as the application of an A1AR agonist to the hair follicle or scalp, one can limit, reduce or prevent as that term is defined herein the traction alopecia-inducing effects of such hairstyles or factors despite the ongoing traction involved.
  • This preventive approach permits one to wear a hairstyle, helmet, etc., that would normally have a high risk of inducing traction alopecia without actually suffering the traction-related hair loss.
  • pilomotor stimulation Various aspects of the technology described herein involve pilomotor stimulation.
  • the measurement or detection of pilomotor stimulation can be performed, at its simplest, by observation of the area at the base of the hair shaft - an agent or treatment that induces arrector pili contraction causes the hair follicle to "stand up” and causes puckering of the skin around the hair shaft commonly referred to as "goose bumps.”
  • an agent or treatment that induces arrector pili contraction causes the hair follicle to "stand up” and causes puckering of the skin around the hair shaft commonly referred to as "goose bumps.”
  • the agent if an agent is applied and the hair stands up, goose bumps form, or both, the agent has stimulated the arrector pili.
  • Measurement of the strength of arrector pili muscle contraction can be performed, if necessary, via myograph adapted for that purpose. Examples are described in, e.g., Zeveke & Gladysheva, Bull.
  • Trichotillometry the reliability and practicality of hair pluckability as a method of nutritional assessment.
  • Trichotillometry the quantitation of hair pluckability as a method of nutritional assessment.
  • Traction alopecia is a form of alopecia, or gradual hair loss, caused primarily by pulling force applied to the hair.
  • Several different hair styles and hair extensions can cause or exacerbate traction alopecia.
  • certain styles or braiding patterns that pull the hairline have been shown to cause traction alopecia.
  • Particularly tight braids, barrettes, or the installation of hair extensions can exert sufficient chronic force on the hair follicles to cause traction alopecia.
  • traction alopecia has a mechanical origin based on the force on the hair. For example, chronic pulling on the hair follicles can cause inflammation. Eventually, follicular scarring and permanent alopecia can occur from prolonged pulling.
  • each follicular unit contains a smooth muscle anchoring the hair to the epidermis.
  • the smooth muscle is relaxed as illustrated in Figure 1A , the muscle does not supply much restraining force and the follicle can be removed easily.
  • the smooth muscle or arrector pili (AP) contracts as illustrated in Figure 1B , the follicle stands up and is restrained by additional force from the smooth muscle rather than just primarily the surrounding connective tissue of the dermis.
  • the smooth muscle can provide more retention force in opposition to a force that would pull on the hair to dislodge the follicle if it is contracted.
  • the arrector pili (AP) muscle by contracting the arrector pili (AP) muscle, the root can be more firmly grounded into the dermis of the skin preventing the mechanical strain from damaging the root and dermis, i.e. requiring a larger epilation force for removal of the hair follicle. This would prevent the chronic stressing from pulling of the hair observed in different hairstyles from doing as much damage to the root, and thereby would prevent or reduce the risk of developing traction alopecia.
  • the technology described herein relates to the reduction of the force exerted on the root of a hair.
  • this "reduction" in force is more akin to providing a better balancing force against a traction on the hair itself - that is, the treatments described herein will not necessarily reduce the amount of traction on the hair, but by stimulating the contraction of the arrector pili muscles, the treatments provide a force that at least partially counters the effect of the traction or pulling force, thereby protecting the root against the epilatory effect of the traction.
  • a patient is wearing a hair extension, wig, a tightly woven or pulling hairstyle, combing their hair, or engaging in other behavior that pulls back on the follicles of the hair.
  • methods for contracting the AP muscle including application of a pharmaceutical composition containing an A1AR agonist, electrical stimulation of the hair follicles and others.
  • the invention concerns treating, reducing or preventing hair loss from disorders such as traction alopecia, androgenic alopecia (also known as androgenetic alopecia), alopecia areata, and alopecia universalis, and hair loss due to hair brushing, combing, etc, comprising topical administration to a person in need thereof of a therapeutically effective amount of an A1AR agonist.
  • the invention concerns a method for the reduction of the force exerted on a root of a hair comprising topical administration to a person in need thereof of a therapeutically effective amount of an A1AR agonist.
  • the invention concerns a method for increasing hair epilation force comprising topical administration to a person in need thereof of a therapeutically effective amount of an A1AR agonist.
  • the invention concerns a cosmetic method for piloerecting hair or raising hair comprising topical administration to a person in need thereof of a therapeutically effective amount of an A1AR agonist.
  • the therapeutically effective amount of the agent administered, such as the A1AR agonist is a pilomotor effective amount.
  • the therapeutic agent, such as the A1AR agonist is applied to a skin section, such as a section of the scalp, that contains at least one hair follicle.
  • the at least one hair follicle is under tension.
  • A1AR agonists may be administered to the hair follicle or scalp to promote contraction of the AP muscle and thereby reduce, treat or prevent alopecia and the other disorders discussed herein. It is specifically contemplated that an A1AR agonist or any other agonist of smooth muscle contraction known in the art or disclosed herein can be administered to the hair follicle or the scalp in combination with an agent that retards systemic absorption of the agent across the dermis. In this manner, agents that might otherwise have unwanted systemic effects can be used to treat, reduce or prevent alopecia or other disorders discussed herein while avoiding such systemic side effects.
  • agents for topical administration in a manner that avoids systemic absorption is discussed in detail in U.S. 2009/0068287 , which is incorporated herein by reference in its entirety.
  • a method for prevention of traction alopecia comprising: applying a therapeutically effective amount, such as a pilomotor effective amount, of an A1AR agonist to the scalp to an area with a group of follicles that will experience a pulling force from a hair augmentation device; and attaching the hair augmentation device to the group of follicles.
  • the hair augmentation device is a hair extension or extensions.
  • the hair augmentation device is a weave.
  • the hair augmentation device is a barrette.
  • a method of reducing hair shedding such as occurs during brushing, combing, weaving, flat ironing, showering, curling, wift, attaching hair extensions or wigs, trading, pony tails, or cosmetic procedures, the method comprising applying a therapeutically effective amount, such as a pilomotor effective amount, of an A1AR agonist topically to a portion of skin that includes at least one hair follicle.
  • a therapeutically effective amount such as a pilomotor effective amount
  • the A1AR agonist is present on a brush or comb that may then be used to administer the therapeutic agent such as the A1AR agonist.
  • the A1AR agonist is applied to the skin prior to the brushing or combing.
  • the cosmetic procedure is selected from the group consisting of brushing, braiding, flat ironing, and combinations of two or more thereof.
  • the therapeutic agent such as the A1AR agonist, may be topically applied once, twice, or more often per day. In another embodiment, the A1AR agonist is applied to the skin twice daily. In another embodiment, the A1AR agonist is applied to the skin prior to the cosmetic procedure.
  • a method for treatment of trichotillomania comprising applying a pilomotor effective amount of an A1AR agonist topically to a portion of skin that includes at least one hair follicle.
  • the disclosure also concerns evaluating an individual for susceptibility to treatment according to the methods disclosed herein.
  • the method comprises (1) applying an A1AR agonist (e.g., without limitation, synephrine) on a site on the skin of a person; and (2) 30 to 60 minutes after applying, observe whether the person's skin shows goosebumps or pilioerection at the site; wherein if pilioerection or goosebumps are observed, diagnosing the person as likely to be a successful candidate for use of the alpha 1 adrenergic receptor agonist for any of the many methods of treatment or prevention described herein.
  • an A1AR agonist e.g., without limitation, synephrine
  • the step of application to the skin may be, in one embodiment, applying a bandage or patch coated with the alpha 1 adrenergic receptor agonist to the person's arm or thigh.
  • the agonist is synephrine or phenylephrine.
  • the therapeutic agents particularly the A1AR agonists, described herein and used in the present methods may be formulated into compositions according to the knowledge of one of skill in the art.
  • the A1AR agonist or other stimulator of AP muscle contraction is formulated for topical slow or prolonged release.
  • the AP stimulating agent is encapsulated for slow release and integrated into a hair extension.
  • the A1AR agonist or other stimulator of AP muscle contraction is formulated in a shampoo (which can reduce hair shedding during hair brushing), a foam, ointment, spray, solution, gel, slow release capsule, oral tablet, or any similar compound or delivery vehicle or methodology.
  • Topical application is preferred.
  • the composition is formulated in a topical cream.
  • the composition is formulated in a hair styling product selected from the group consisting of a styling gel, a styling foam, and a hair conditioner.
  • the composition may comprise an exfoliating agent to promote abrasion of the surface of the scalp.
  • exfoliating agent include (1) inorganic and/or metallic particles such as: boron nitride, in body-centered cubic form (Borazon®); aluminosilicate (e.g.
  • nepheline zircon
  • mixed oxides of aluminum such as emery; zinc oxide; aluminum oxides such as aluminas or corundum; titanium oxide; titanium oxide coated mica; carbides, in particular silicon carbide (carborundum); or other metal oxides; metals, and metal alloys such as iron shot, steel shot, and in particular perlite; silicates such as glass, quartz, sand, or vermiculite; calcium carbonate (e.g. Bora-Bora sand or Rose de Brignoles sand) or magnesium carbonate; sodium chloride; pumice stone; amorphous silica; diamond; ceramics, and (2) organic particles such as: fruit stones, in particular apricot stones, e.g.
  • Scrubami® apricot wood cellulose, e.g. ground bamboo stem; coconut shell, e.g. coconut exfoliator; polyamides, in particular Nylon-6; sugars; plastic microbeads, e.g. polyethylenes or polypropylenes; ground walnut; ground apricot seed; ground shells, and (3) mixed particles associating organic and inorganic compounds, and particles coated in the above compounds.
  • the exfoliating agents may be in the form of microbeads of less than five millimeters in its largest dimension that have an exfoliating effect.
  • the composition comprising an A1AR agonist can be formulated as a drug. In one embodiment, the composition comprising an A1AR agonist can be formulated as a cosmetic product.
  • the AP muscle can be contracted via electrical stimulation to the scalp.
  • the stimulation can be controlled by a battery and control unit embedded into a hair extension, or in, e.g., a hair brush or comb.
  • the control unit can contain an accelerometer to detect the optimal time to contract the AP muscles based on the posture of the subject or the subject's hair.
  • the amount of therapeutic agent present in the composition may be determined by one of skill in the art using known methodologies.
  • the A1AR agonist or other stimulator of AP muscle contraction is present in the composition in a concentration from about 0.20% to 0.30%, or about 0.25% by weight.
  • the therapeutic agent such as an A1AR agonist is present in the composition in a concentration of about 0.25%, 0.33%, 0.5%, 1%, 2%, 2.5%, or 10% by weight.
  • the therapeutic agent such as the A1AR agonist
  • the topical composition for use in the methods disclosed herein in a concentration from about 0.1% to 35%, about 1.0% to 30%, about 0.2% to 30%, about 0.2% to 25% , about 0.2% to 20%, about 0.2% to 15%, about 0.2% to 10%, about 0.2% to 5%, about 0.2% to 4%, about 0.2% to 3%, about 0.2% to 2%, about 0.2% to 1%, about 10.0% to 30%, about 15.0% to 30%, about 20.0% to 30%, about 10% to 20%, about 10% to 15%, about 15% to 20%, about 15% to 60%, about 20% to 60%, about 50% to 60%, and about 45% to 55% by weight.
  • a concentration of about 25% to 60%, 30% to 50%, 30% to 60%, 25% to 30%, 40% to 50%, or 50% to 55% by weight of the total weight of the composition is desirable.
  • the composition comprises an A1AR agonist in a concentration of about 0.25%, about 0.33%, about 0.5%, about 1%, about 2%, about 2.5%, about 3.0%, about4.0%, about 10%, about 15%, about 20%, or about 25% by weight.
  • compositions used in the present disclosure may be formulated with a preservative such as EDTA (0.1-0.5% by weight of the formulation) and/or sodium metabisulfite (0.1-0.5% by weight of the formulation).
  • the composition includes a penetration enhancer, such as a penetration enhancer selected from one or more of the group consisting of alcohols, glycols, fatty acids, fatty esters, fatty ethers, occlusive agents, surface active agents, dimethylaminopropionic acid derivatives, terpenes, sulfoxides, cyclic ethers, amides, and amines.
  • a penetration enhancer such as a penetration enhancer selected from one or more of the group consisting of alcohols, glycols, fatty acids, fatty esters, fatty ethers, occlusive agents, surface active agents, dimethylaminopropionic acid derivatives, terpenes, sulfoxides, cyclic ethers, amides, and amines.
  • the composition may be packaged in a kit with an applicator for application to the skin.
  • the invention is also directed to a kit comprising a composition of the therapeutic agent, such as an A1AR agonist, and an applicator, and to a kit comprising a composition of the therapeutic agent, such as an A1AR agonist, and a hair brush or comb, particularly a brush or comb that provides exfoliating effect on the scalp such that there is light abrasion after its use that enhances penetration of the therapeutic agent to the AP muscle.
  • the therapeutic agent is provided in a metered dose applicator that provides for a fixed volume of the composition to be administered with each administration, such as 1 ml of the topical composition per administration.
  • A1AR agonist or other compound that causes contraction directly or indirectly of the AP muscle.
  • Suitable A1AR agonists can be utilized including phenylephrine, cirazoline, desvenlafaxine, etilfrine, metaraminol, methoxamine, naphazoline, oxymetazoline, pseudoephrine, m-synephrine, p-synephrine, synephrine, octopamine, hordenine, tetrahydrozoline, isometheptene, metaraminol, nicergoline, ergonovine, levonordefrin, phendimetrazine, methoxamine, midodrine, clonidine, pergolide, xylometazoline, droxidopa, epinephrine, mephentermine, 4-methoxyamphetamine, Benzphetamine, Naphazol
  • derivatives of A1AR agonists can be utilized including derivatives of the compounds mentioned above.
  • a prodrug that is activated to become an A1AR agonist can be utilized.
  • midodrine is one such prodrug.
  • a particular prodrug can be activated by endogenous enzymes in the scalp such as Caspase-l when follicular inflammation is present, e.g., at the location of application of a hair extension.
  • the A1AR agonist is synephrine.
  • the A1ARA is phenylephrine or synephrine, including compositions comprising the 1-enantiomer of synephrine, which is R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol, that are essentially free of other enantiomers of synephrine, or in which less than 30%, 25%, 20%, 15%, 10%, 12%, 5%, 3%, 1%, or 0.5% by weight of the synephrine present in the composition is a different enantiomer.
  • the synephrine enantiomer R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol may be obtained from natural bitter orange extract.
  • the therapeutic agent is derived from bitter orange, Citrus aurantium, or is an extract of bitter orange, such as a bitter orange extract that contains 95%, 96%, 97%, 98%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or 2% by weight or from 5-10%, 10-15%, 5-15%, 20-25%, 15-20%, 25-30%, 30-35%, 35-40%, 40-45%, 45-55%, 50-60%, 60-70%, 70-80%, 80-90%, 85-95%, or 90-99% of one enantiomer of synephrine, R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol.
  • an extract of bitter orange such as a bitter orange extract that contains 95%, 96%, 97%, 98%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 9%, 8%, 7%, 6%,
  • Extracts of bitter orange contain high levels of only one synephrine enantiomer, namely, R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol, and are preferred for use in the present methods and compositions of the disclosure.
  • the compositions of the present invention contain 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 16%, 27%, 28%, 29%, 30% or 31% by weight of bitter orange extract, such as an extract that contains 3-5%, 5-10%, 6%, 9%, 10-15%, 15-20%, 20-40%, 40-60%, 60-80%, or 80-95% synephrine, or the composition contains from about 5-10%, 10-15%, 15-20%, 25-30% or 30-40% by weight of bitter orange extract, such as an extract containing from about 3-5%, 5-10%, 6%, 9%, 10-15%, 15-20%, 20-30%, 30-50%, 50-60%, 60-70%, 70-80%, 80-90% or 80-99% synephrine.
  • bitter orange extract such as an extract that contains 3-5%, 5-10%, 6%, 9%, 10-15%, 15-20%, 20-30%, 30-50%, 50-60%,
  • compositions of the present invention contain 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 16%, 27%, 28%, 29%, 30% or 31% by weight of a bitter orange extract, wherein the extract contains 50-90%, 50-60%, 60-70%, 70-80%, 80-90%, 85-95% or 90-99% synephrine and substantially all of the synephrine in the extract is the enantiomer R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol.
  • the A1AR agonist is phenylephrine, or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration of 0.25% to 40%, 0.25% to 25% by weight, or 0.5% to 22.5% by weight, or 0.75% to 20% by weight, or 1% to 17.5% by weight, or 1.5% to 15% by weight, or 2% to 14.5% by weight, or 2.5% to 14% by weight, or 5% to 13.5% by weight, or 7.5% to 12.5% by weight, or 8% to 12% by weight, or 8.5% to 11.5% by weight, or 9% to 11% by weight, or 9.25% to 10.75% by weight, or 9.5% to 10.5% by weight, or 9.6% to 10.4% by weight, or 9.7% to 10.3% by weight, or 9.8% to 10.2% by weight, or 9.9% to 10.1% by weight, or 9.95% to 10.05% by weight, or 9.96% to 10.04% by weight, or 9.97% to 10.03% by weight, or 9.98% to 10.02% by weight, or 9.
  • the A1AR agonist is phenylephrine, or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration at a range of 0.25%, 0.5%, 0.75%, 1%, 1.5%, 2%, 2.5%, 5%, 7.5%, 8%, 8.5%, 9%, 9.25%, 9.5%, 9.6%, 9.7%, 9.8%, 9.9%, 9.95%, 9.96%, 9.97%, 9.98%, or 9.99% by weight as the lower weight limit of the range to an upper weight limit of 10.01%, 10.02%, 10.03%, 10.04%, 10.05%, 10.1%, 10.2%, 10.3%, 10.4%, 10.5%, 10.75%, 11%, 11.5%, 12%, 12.5%, 13.5%, 14%, 14.5%, 15%, 17.5%, 20%, 22.5%, 25%, 30%, 35%, 40%, 45%, or 50% by weight (e.g., a range of 0.25% to 10.01%, 0.25% to 10.02%, 0.5% to 10.01%
  • the A1AR agonist is phenylephrine, or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration of 0.25% by weight, or 0.5% by weight, or 0.75% by weight, or 1% by weight, or 1.5% by weight, or 2% by weight, or 2.5% by weight, or 5% by weight, or 7.5% by weight, or 8% by weight, or 8.5% by weight, or 9% by weight, or 9.25% by weight, or 9.5% by weight, or 9.6% by weight, or 9.7% by weight, or 9.8% by weight, or 9.9% by weight, or 9.95% by weight, or 9.96% by weight, or 9.97% by weight, or 9.98% by weight, or 9.99% by weight, or 10% by weight, or 10.01% by weight, or 10.02% by weight, or 10.03% by weight, or 10.04% by weight, or 10.05% by weight, or 10.1% by weight, or 10.2% by weight, or 10.3% by weight, or 10.4% by weight, or 10.5% by weight, or 10.5% by
  • the composition comprises an A1AR agonist that is synephrine, or a pharmaceutically acceptable salt or hydrate thereof, or that comprises one enantiomer of synephrine, namely R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol and is substantially free of other enantiomer(s) of synephrine or has less than 30%, 25%, 20%, 15%, 10%, 12%, 5%, 3%, 1%, or 0.5% by weight of the synephrine present in the composition as a different enantiomer, wherein the synephrine is present in the composition in a concentration of 30% to 70% by weight, or 35% to 65% by weight, or 37.5% to 62.5% by weight, or 40% to 60% by weight, or 42.5% to 57.5% by weight, or 45% to 55% by weight, or 45.5% to 54.5% by weight, or 46% to 54% by weight, or 46.5% to 53.5% by weight, or 47%
  • the composition comprises an A1AR agonist that is synephrine, or a pharmaceutically acceptable salt or hydrate thereof, or that comprises one enantiomer of synephrine, namely R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol and is substantially free of other enantiomer(s) of synephrine or has less than 30%, 25%, 20%, 15%, 10%, 12%, 5%, 3%, 1%, or 0.5% by weight of the synephrine present in the composition as a different enantiomer, wherein the synephrine is present in the composition in a concentration of 20% by weight, or 25% by weight, or 30% by weight, or 35% by weight, or 37.5% by weight, or 40% by weight, or 42.5% by weight, or 45% by weight, or 45.5% by weight, or 46% by weight, or 46.5% by weight, or 47% by weight, or 47.5% by weight, or 48% by weight, or 48.25%
  • the composition comprises an A1AR agonist that is R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol substantially free of the other enantiomer of synephrine (or having less than 25%, 20%, 15%, 10%, 5%, 1% or 0.1% of the other enantiomer of synephrine) or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration of 20% by weight, or 21% by weight, or 25% by weight, or 26% by weight, or 30% by weight, or 35% by weight, or 37.5% by weight, or 40% by weight, or 42.5% by weight, or 45% by weight, or 45.5% by weight, or 46% by weight, or 46.5% by weight, or 47% by weight, or 47.5% by weight, or 48% by weight, or 48.25% by weight, or 48.5% by weight, or 48.75% by weight, or 49% by weight, or 49.25% by weight, or 49.5% by weight, or 49.5% by
  • the composition comprises an A1AR agonist that is synephrine, or a pharmaceutically acceptable salt or hydrate thereof, or that comprises one enantiomer of synephrine, namely R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol and is substantially free of other enantiomer(s) of synephrine or has less than 30%, 25%, 20%, 15%, 10%, 12%, 5%, 3%, 1%, or 0.5% by weight of the synephrine present in the composition as a different enantiomer, wherein the synephrine is present in the composition in a concentration of 10% to 60% by weight, or 12.5% to 50% by weight, or 10% to 50% by weight, or 15% to 40% by weight, or 20% to 30% by weight, or 20% to 40% by weight, or 17.5% to 30% by weight, or 20% to 25% by weight, or 20.5% to 24.5% by weight, or 21% to 24% by weight, or 21.5% to 23.5% by weight, or
  • the composition comprises an A1AR agonist that is synephrine, or a pharmaceutically acceptable salt or hydrate thereof, or that comprises one enantiomer of synephrine, namely R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol and is substantially free of other enantiomer(s) of synephrine or has less than 30%, 25%, 20%, 15%, 10%, 12%, 5%, 3%, 1%, or 0.5% by weight of the synephrine present in the composition as a different enantiomer, wherein the synephrine is present in the composition in a concentration of 10% by weight, or 12.5% by weight, or 15% by weight, or 17.5% by weight, or 20% by weight, or 20.5% by weight, or 21% by weight, or 21.5% by weight, or 21.75% by weight, or 22% by weight, or 22.1% by weight, or 22.2% by weight, or 22.3% by weight, or 22.4% by weight to 22.
  • the composition comprises one enantiomer of synephrine, namely R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol, and is substantially free of other enantiomer(s) of synephrine or has less than 30%, 25%, 20%, 15%, 10%, 12%, 5%, 3%, 1%, or 0.5% by weight of the synephrine present in the composition as a different enantiomer, wherein the R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol is present in the composition in a concentration of 20% to 25% by weight.
  • the A1AR agonist is oxymetazoline, or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration of 0.01% to 2% by weight, or 0.02% to 1.75% by weight, or 0.03% to 1.5% by weight, or 0.04% to 1.25% by weight, or 0.05% to 1% by weight, or 0.1% to 0.9% by weight, or 0.15% to 0.85% by weight, or 0.2% to 0.8% by weight, or 0.25% to 0.75% by weight, or 0.3% to 0.7% by weight, or 0.35% to 0.65% by weight, or 0.4% to 0.6% by weight, or 0.41% to 0.59% by weight, or 0.42% to 0.58% by weight, or 0.43% to 0.57% by weight, or 0.44% to 0.56% by weight, or 0.45% to 0.55% by weight, or 0.46% to 0.54% by weight, or 0.47% to 0.53% by weight, or 0.48% to 0.52% by weight, or 0.49% to 0.51% by weight
  • the A1AR agonist is oxymetazoline, or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration of 0.01% by weight, or 0.02% by weight, or 0.03% by weight, or 0.04% by weight, or 0.05% by weight, or 0.1% by weight, or 0.15% by weight, or 0.2% by weight, or 0.25% by weight, or 0.3% by weight, or 0.35% by weight, or 0.4% by weight, or 0.41% by weight, or 0.42% by weight, or 0.43% by weight, or 0.44% by weight, or 0.45% by weight, or 0.46% by weight, or 0.47% by weight, or 0.48% by weight, or 0.49% by weight to 0.51% by weight, or 0.52% by weight, or 0.53% by weight, or 0.54% by weight, or 0.55% by weight, or 0.56% by weight, or 0.57% by weight, or 0.58% by weight, or 0.59% by weight, or 0.6% by weight, or 0.65% by weight,
  • the A1ARA is oxymetazoline, or a pharmaceutically acceptable salt or hydrate thereof, in a composition in a concentration of 0.01% by weight, or 0.02% by weight, or 0.03% by weight, or 0.04% by weight, or 0.05% by weight, or 0.1% by weight, or 0.15% by weight, or 0.2% by weight, or 0.25% by weight, or 0.3% by weight, or 0.35% by weight, or 0.4% by weight, or 0.41% by weight, or 0.42% by weight, or 0.43% by weight, or 0.44% by weight, or 0.45% by weight, or 0.46% by weight, or 0.47% by weight, or 0.48% by weight, or 0.49% by weight, or 0.5% by weight, or 0.5 1% by weight, or 0.52% by weight, or 0.53% by weight, or 0.54% by weight, or 0.55% by weight, or 0.56% by weight, or 0.57% by weight, or 0.58% by weight, or 0.59% by weight, or 0.6% by weight, or 0.5 1%
  • an A1AR agonist formulated with a carrier or delivery vehicle optimized for delivery of the A1AR agonist to the scalp.
  • An A1AR agonist can be released using several different formulations or release methods including time release, creams, ointments, sprays, capsules, or other release methods.
  • the A1AR agonist can be incorporated into a shampoo for utilization during showering so that when a user brushes their hair, their follicles will be tightly held by the AP muscles to prevent brushing from unnecessarily pulling out healthy hair.
  • the A1AR agonist can be included in ointments or other topical creams that could be applied to the scalp so that it can be slowly absorbed into the skin and stimulate the smooth muscle.
  • the A1AR agonist can be included in a liquid spray or aerosol medium to be applied to the scalp.
  • the A1AR agonist can be incorporated into capsules or other slow release vehicles that would allow the chemical or agent to be slowly released into the dermis of the scalp.
  • Capsules or vehicles that encapsulate the A1AR agonist can include, but are not limited to, liposomes, non-ionic liposomes, niosomes, novasome I, erythromycin-Zn complex, microspheres, nanoparticles, solid lipid nanoparticles, and nanoemulsions. In some embodiments, this can include a gel or foam that is applied to the scalp. It is specifically contemplated that the A1AR agonist can be formulated in hair care products such as styling gel, styling foam, hair conditioner, hair serum, a hair mask, etc.
  • any of the aforementioned A1AR agonist can be applied by a user before the application of a hair extension device or other device or condition that exerts force on the hair follicle.
  • an A1AR agonist can be used routinely (e.g. twice daily) after such a device has been installed. Routine use of an A1AR agonist would be indicated as a prophylactic against traction alopecia for users of a hair extension device or other device that exerts force on the hair follicle.
  • Creams or other formulations with different A1AR agonists can be applied prior to a user utilizing a hair piece or brushing the hair.
  • a hair piece or hair extensions can contain pads or other absorbent material that can absorb A1AR agonist in a foam or cream applied prior to application to a user's head.
  • slow release capsules can be incorporated into the hair extensions or hair pieces, or can be included in barrettes.
  • barrettes will include pads with an absorbent layer for application of A1AR agonist cream or other A1AR agonist topical formulation.
  • Efficacy of treatment to treat or prevent traction alopecia can be determined by monitoring the density of hairs on a given area of the subject's body, e.g., a given area of the scalp. If the rate of hair loss is reduced, e.g., by 10% or more following treatment, the treatment is effective for the prevention of traction alopecia. Similarly, if hair density remains the same, despite ongoing traction that would normally have been expected to cause traction alopecia, the treatment is effective for the prevention of traction alopecia. If the density of hair increases, e.g., by 5% or more, e.g., by 10% or more following treatment and despite ongoing traction, the treatment is also considered effective for the treatment and/or prevention of traction alopecia.
  • alopecia can benefit from the technology described herein.
  • the technology described herein can be applicable to prevent or treat androgenic alopecia.
  • the AP muscle degenerates in the process of androgenic alopecia (reviewed, e.g., in Torkamani et al., Int. J. Trichology 6:88-94 (2014 )); without wishing to be bound by theory, it is contemplated that regular stimulation of AP muscle contraction may slow or reduce the loss of the muscle and thereby benefit the treatment or prevention of androgenic alopecia.
  • the technology described herein can be broadly applicable to any type of condition of which at least one hair follicle is under tension.
  • the A1AR agonist compositions or other agents that stimulate AP muscle contraction as described herein it is contemplated that one can limit or reduce hair shedding under such conditions.
  • the condition of which at least one hair follicle is under tension is brushing or combing.
  • the technology described herein relates to a method of reducing hair shedding during brushing or combing.
  • reducing hair shedding means that the amount of hair shedding from a subject is reduced by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, or more, as compared to what would be expected in the absence of the method.
  • An A1AR agonist or other agent that stimulates AP muscle contraction can be present on the brush or comb used for the brushing or combing.
  • the A1AR agonist or other agent can be applied to the brush or comb prior to brushing or combing, e.g., in the form of a liquid, gel, cream or spray.
  • the brush or comb can dispense the A1ARA or other agent.
  • Agents that promote the contraction of the AP muscle can optionally be administered by iontophoresis, which uses an electric field to drive the passage of ionic agents or drugs into the skin.
  • iontophoresis has been used to deliver agents such as phenylephrine to the skin to stimulate AP muscle contraction (See, e.g., Siepmann et al., Neurology April 25, 2012; 78(Meeting Abstracts 1): P05.197 ).
  • a brush or comb can incorporate an iontophoresis device, which can dispense the A1ARA or other agent and/or be used for transdermal delivery of the agent(s).
  • the iontophoresis device can comprise one or more metal contacts.
  • the iontophoresis device can comprise one or more compartments for containing the A1AR agonist or other agent(s).
  • the condition in which at least one hair follicle is under tension is a hair-related cosmetic procedure.
  • the technology described herein relates to a method of reducing hair shedding during a hair-related cosmetic procedure.
  • hair-related cosmetic procedures include, but are not limited to, brushing, braiding, flat ironing, and combinations thereof.
  • the condition in which at least one hair follicle is under tension is trichotillomania, a disorder characterized by the compulsive urge to pull out one's hair. Accordingly, to the extent that increasing the force required to remove the hair can help counter hair loss due to this condition, the stimulation of AP muscle contraction as described herein can provide a method to reduce the hair loss.
  • the AP muscle can be contracted via electrical stimulation to the scalp or dermis of the skull.
  • the electrical stimulation can be controlled, e.g., by a unit contained in a brush or a comb, or, e.g., embedded in a hair extension.
  • the control unit can contain an accelerometer to detect the optimal time to contract the AP muscles based on the posture of the subject or the subject's hair.
  • a strain or other force gauge attached to a portion of a hair extension can test the force pulling on the patient's hair. Then, the electrical stimulator could vary the amount of current, voltage or other component of the electrical stimulation applied to vary the strength of smooth muscle contraction based on the amount of force pulling on the hair at a certain time.
  • control unit can deliver a standard amount of current to the hair in order to reach the electrical threshold for contraction of the AP muscle. This can advantageously minimize the amount of current being applied to the scalp overall and the amount of electricity. Accordingly, one advantage of utilizing electrical stimulation to contract the muscle, is that the strength of the contraction can be varied accordingly.
  • the voltage or amplitude of the signal applied to the scalp can be in the range of 35 to 75 volts, 25 to 50 volts, 10 - 30 volts or other suitable ranges to reach the threshold for muscle contraction.
  • the current applied to a scalp by a device as disclosed herein can, in some embodiments, preferably be in the microamps to avoid electrocution of the user.
  • a frequency of 10 KHz to 15 KHz can be applied, or a lower or higher frequency.
  • the pulse length applied will be from 1 to 50 milliseconds, 1 to 100 milliseconds, or other suitable lengths to contract the AP muscle or any other pilomotor effective amount of current.
  • a control unit will automatically pulse the electrical stimulation at random intervals that are enough to keep the AP muscle relatively contracted. In other embodiments, the pulses will be spaced out enough to allow the AP muscle to relax in between pulses.
  • the disclosure also concerns a device for hair augmentation and prevention of traction alopecia comprising: a hair augmentation device; and an electrical stimulation device connected to the hair augmentation device, the electrical stimulation device comprising: a battery; a memory; an electrical stimulation generator; a scalp probe in electrical communication with the electrical stimulation generator for applying an electrical stimulus; and a controller in communication with the battery, memory, and electrical stimulation and memory wherein the controller commands the electrical stimulus generator to output a pilomotor effective amount of electrical stimulus.
  • the pilomotor effective amount of electrical stimulus is between 10 - 100 volts, or between 10 - 15 kHz.
  • the pilomotor effective amount of electrical stimulus is applied for 1 to 100 milliseconds.
  • the pilomotor effective amount of electrical stimulus is applied periodically with rest periods long enough to allow the AP muscle to relax between stimuli. In other embodiments, the pilomotor effective amount of electrical stimulus is applied periodically with rest periods short enough to prevent the AP muscle from relaxing between stimuli.
  • the hair augmentation device may be any product that when applied to the hair exerts a pulling force on the hair.
  • the hair augmentation device may be a hair extension, a weave, or a barrette.
  • a probe or electrical prongs can be attached to a hair extension or other hair piece that would deliver the charge to the scalp.
  • the probe can be connected to a control unit with an on switch, a processor, and memory with firmware or other software instructions for delivering the desired pulses.
  • Different control units can contain more advanced circuitry and algorithms for processing accelerometer or force data and varying the electrical stimulus accordingly.
  • the probe can be connected to any portion of a hair piece using any suitable apparatus and method.
  • agents or approaches can be used to contract the smooth muscle for the prevention or treatment of alopecia, e.g., traction alopecia.
  • alopecia e.g., traction alopecia.
  • any agent or treatment that stimulates AP muscle contraction is of potential use in methods of treating, reducing or preventing alopecia as described herein.
  • the smooth muscle can be contracted by stimulating or activating a cold receptor.
  • a cold receptor can be stimulated, for example, by activating the TRPM8 channel.
  • agents that can stimulate a cold receptor include, but are not limited to, menthol and icilin.
  • Compositions and methods for stimulating a cold receptor are disclosed, for example, in US Patent 4,034,109 .
  • agents that stimulate release of transmitters from these systems can be used to stimulate AP muscle contraction.
  • alpha 1 adrenergic agonists but also cholinergic agonists, including, but not limited to acetylcholine and other neurotransmitters that stimulate smooth muscle contraction are contemplated for use in the methods and compositions described herein.
  • the alpha 1 adrenergic receptor is a G protein-coupled receptor.
  • Agonists of other G protein-coupled receptors e.g., alpha 2 adrenergic receptor
  • alpha 2 adrenergic receptor agonists include, but are not limited to, 4-NEMD, 7-Me-marsanidine, agmatine, apraclonidine, brimonidine, clonidine, detomidine, dexmedetomidine, fadolmidine, guanabenz, guanfacine, lofexidine, marsanidine, medetomidine, methamphetamine, mivazerol, rilmenidine, romifidine, talipexole, tizanidine, tolonidine, xylazine, and xylometazoline.
  • 4-NEMD 7-Me-marsanidine
  • agmatine e.g., apraclon
  • halostachine also known as N-methylphenylethanolamine
  • halostachine is contemplated for use as a therapeutic agent in the methods and compositions described herein to stimulate smooth muscle contraction.
  • agonists described herein also encompass their inorganic or organic salts.
  • Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, succinate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like.
  • compositions described herein can also be used for the treatment of acne. It is known that contraction of the AP muscle plays a role in the secretion of the sebum (see Mahfouz et al., J. Egyptian worn. Dermatol. Soc. 2005, 2, 25-29 ).
  • the compositions can be applied in the form of lotion, cream, spray, or wipe.
  • the compositions can be used in combination with benzoyl peroxide or other topical medications for acne treatment.
  • Example 1 Oxymetazoline HCl at 0.1%, 0.2%, 0.5% by weight
  • oxymetazoline Due to the long acting effect of oxymetazoline it may be beneficial to apply once daily, every other day, or as needed prior to mechanical procedures that may exert epilatory forces on hair follicles.
  • the 10.0% topical phenylephrine solution (Formula C) elicited a clinical response in all subjects while the 5.0% and 7.5% formulations (Formula A and B) failed to elicit a response.
  • the 10.0% topical phenylephrine solution response in the contraction of the arrector-pilomotor muscle was obtained approximately within 20-30 minutes and lasted over 3 hours.
  • phenylephrine hydrochloride to assess the use of topical phenylephrine hydrochloride solution as a novel drug for prevention/reduction of hair loss from mechanical pulling.
  • Excluded subjects were those who experienced uncontrolled hypertension, those who were pregnant or breastfeeding, those who were diagnosed with pattern hair loss, or those who experienced other hair loss in conjunction with female pattern hair loss.
  • Figures 2 and 3 show that application of the 10% phenylephrine hydrochloride solution resulted in reduced hair shedding in 80% of the patients, as compared to the placebo solution containing the vehicle, with the average reduction being approximately 42%.
  • Figures 4 and 5 show that the epliatory force threshold for plucking hair follicles following topical 10% phenylephrine hydrochloride application increased by approximately 172%. Therefore, there is a significant reduction hair loss from mechanical pulling and increase in epilatory force after topical application of 10% phenylephrine hydrochloride.
  • This novel study demonstrates the utility of ⁇ 1-AR agonists in the treatment of traction alopecia and excessive hair loss resulting from mechanical cosmetic procedures.
  • Patients Fifteen female subjects, ages 18-40, were included in the study. Subjects were recruited based on their frequent use of traumatic hair care practices, such as, tight braids, head scarves, ponytails, extensions, hair rollers, hair weaves and heated styling appliances such as blow dryers, flat irons, heat setters and curling irons. Subjects with uncontrolled hypertension, that were pregnant or breastfeeding, had been diagnosed with pattern hair loss or with other hair loss in conjunction with female pattern hair loss were excluded from the study. Prior to initiating the study, the efficacy of the 10% phenylephrine solution was tested by applying a small aliquot (50 ⁇ L) of the solution to the forearm of three subjects. Piloerection and blanching were visible after 30 minutes; the effect lasted for approximately 2-3 hours.
  • traumatic hair care practices such as, tight braids, head scarves, ponytails, extensions, hair rollers, hair weaves and heated styling appliances such as blow dryers, flat irons, heat setters and curling irons.
  • a hand-held spring dynamometer or "trichotillometer” was used (8).
  • the trichotillometer records the maximum force threshold, in grams, required to pluck a single hair from the scalp; the performance and statistical variance of the instrument have been reported previously (8-10). Force measurements were performed using the trichotillometer on 10 subjects. The frontal area of scalp was divided into two 8x10 cm2 areas. On the right side 0.5 mL of a placebo vehicle was applied. On the left side, 0.5 mL a 10% phenylephrine solution was applied. After 45 minutes, ten hairs were plucked from each of the target areas with the trichotillometer.

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Claims (15)

  1. Alpha-1-Adrenozeptoragonist zur Anwendung in der Behandlung oder Prävention von Traktionsalopezie, umfassend das topische Auftragen einer Zusammensetzung, die eine pilomotorisch wirksame Menge eines Alpha-1-Adrenozeptoragonisten umfasst, auf einen Teil der Kopfhaut, der zumindest einen Haarfollikel einschließt,
    wobei die Zusammensetzung einen Alpha-1-Adrenozeptoragonisten umfasst, der Synephrin oder ein pharmazeutisch annehmbares Salz oder Hydrate dessen ist.
  2. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 1, wobei der zumindest eine Haarfollikel unter Spannung ist oder der Teil der Haut dem Risiko ausgesetzt ist, Traktionsalopezie zu entwickeln.
  3. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 1, wobei das Synephrin in der Zusammensetzung in einer Konzentration von 5 bis 60 Gew.-% enthalten ist.
  4. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 1, wobei die Zusammensetzung das I-Enantiomer des Synephrin umfasst, das R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol ist und weniger als 10 Gew.-% andere Enantiomere des Synephrin enthält, wobei R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol vorzugsweise zu 20 bis 40 Gew.-% in der Zusammensetzung enthalten ist.
  5. Alpha-1-Adrenozeptoragonist zur Anwendung in einem Verfahren zum Reduzieren des Haarlassens aufgrund von mechanischem Ziehen, das Handlungen des Bürstens, Kämmens oder Duschens involviert, wobei das Verfahren das topische Auftragen einer Zusammensetzung umfasst, die eine pilomotorisch wirksame Menge eines Alpha-1-Adrenozeptoragonisten, der Synephrin oder ein pharmazeutisch annehmbares Salz oder Hydrate dessen ist, auf einen Teil der Kopfhaut umfasst, der zumindest einen Haarfollikel einschließt.
  6. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 5, wobei die Zusammensetzung vor dem Bürsten oder Kämmen auf die Haut aufgetragen wird oder wobei der zumindest eine Haarfollikel unter Spannung ist.
  7. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 5, wobei das Synephrin in der Zusammensetzung in einer Konzentration von 5 bis 60 Gew.-% enthalten ist.
  8. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 5, wobei die Zusammensetzung das I-Enantiomer des Synephrin umfasst, das R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol ist und weniger als 10 Gew.-% andere Enantiomere des Synephrin enthält, wobei R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol vorzugsweise zu 20 bis 40 Gew.-% in der Zusammensetzung enthalten ist.
  9. Alpha-1-Adrenozeptoragonist zur Anwendung in einem Verfahren zum Erhöhen der Haarentfernungskraft, um Effekte aufgrund von mechanischen Kräften, die das Haar ziehen, zu mildern, wobei das Verfahren das topische Auftragen einer Zusammensetzung, die eine pilomotorisch wirksame Menge eines Alpha-1-Adrenozeptoragonisten umfasst, auf einen Teil der Kopfhaut einer Person umfasst, der zumindest einen Haarfollikel einschließt,
    wobei die Zusammensetzung einen Alpha-1-Adrenozeptoragonisten umfasst, der Synephrin oder ein pharmazeutisch annehmbares Salz oder Hydrate dessen ist.
  10. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 9, wobei die Person sich vor, während oder nachdem die Zusammensetzung aufgetragen wird, einer kosmetischen Behandlung des Haars unterzieht, ausgewählt aus der Gruppe, die aus Flechten, Glätten, Befestigen eines Haar weave, Befestigen einer Haarverlängerung oder dem Zurückbinden des Haars in einen Pferdeschwanz besteht, oder der Alpha-1-Adrenozeptoragonist einmal täglich oder zweimal täglich auf die Haut aufgetragen wird.
  11. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 9, wobei das Synephrin in der Zusammensetzung in einer Konzentration von 5 bis 60 Gew.-% enthalten ist.
  12. Alpha-1-Adrenozeptoragonist zur Anwendung nach Anspruch 9, wobei die Zusammensetzung das I-Enantiomer des Synephrin umfasst, das R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol ist und weniger als 10 Gew.-% andere Enantiomere des Synephrin enthält, wobei R-(-)-4-[1-hydroxy-2-(methylamino)ethyl]phenol vorzugsweise zu 20 bis 40 Gew.-% in der Zusammensetzung enthalten ist.
  13. Alpha-1-Adrenozeptoragonist zur Anwendung in der Prävention von Traktionsalopezie, wobei die Anwendung umfasst:
    Auftragen einer Zusammensetzung, die eine pilomotorisch wirksame Menge eines Alpha-1-Adrenozeptoragonisten umfasst, auf die Kopfhaut auf einen Bereich mit einer Gruppe von Follikeln, die eine Zugkraft von einem Haarverstärkungsmittel erfahren werden; und Anbringen des Haarverstärkungsmittels an die Gruppe von Follikeln, wobei die Zusammensetzung einen Alpha-1-Adrenozeptoragonisten umfasst, der Synephrin oder ein pharmazeutisch annehmbares Salz oder Hydrate dessen ist.
  14. Kosmetisches Verfahren zum Aufstellen der Körperhaare oder Aufrichten von Haar, umfassend die topische Anwendung einer therapeutisch wirksamen Menge an Synephrin bei einer Person, die dieses benötigt.
  15. Synephrin oder eine Zusammensetzung, die Synephrin oder ein pharmazeutisch annehmbares Salz oder Hydrat dessen umfasst, zur Anwendung in der Behandlung oder Prävention von Traktionsalopezie.
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Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102476626B1 (ko) 2014-11-14 2022-12-09 폴리 인터내셔널 탈모증을 예방하기 위한 시스템 및 방법
US10064816B2 (en) 2015-06-11 2018-09-04 ReJoy Treatment of sexual dysfunction
KR102493627B1 (ko) * 2015-11-26 2023-01-31 코웨이 주식회사 호르데닌을 유효성분으로 함유하는 피부암 예방 또는 치료용 약학 조성물
WO2018093370A1 (en) * 2016-11-17 2018-05-24 Follea International System and method for preventing alopecia
WO2018218012A1 (en) 2017-05-24 2018-11-29 Follea International Synephrine compositions
US11890278B2 (en) 2018-01-17 2024-02-06 University Of Florida Research Foundation, Incorporated Betel quid cessation therapy with nicotine and pilocarpine
WO2020023084A1 (en) * 2018-07-26 2020-01-30 Applied Biology, Inc. Taar receptor agonists for the treatment of alopecia
WO2021167097A1 (ja) * 2020-02-19 2021-08-26 株式会社 資生堂 立毛筋細胞の賦活化による老化改善方法
WO2024118094A1 (en) * 2022-11-29 2024-06-06 Follea International System and method for preventing alopecia

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4034109A (en) 1973-01-18 1977-07-05 Wilkinson Sword Limited Compounds having a physiological cooling effect and compositions containing them
US4853216A (en) * 1987-04-02 1989-08-01 Bristol-Myers Company Process and composition for the topical application of alpha1 adrenergic agonist for pilomotor effects
US5055456A (en) 1989-01-27 1991-10-08 American Cyanamid Co. Anti-alopecia composition
US5750141A (en) 1993-04-08 1998-05-12 The University Of Queensland Administration of vaso-active agent and therapeutic agent
CA2154979A1 (en) 1995-07-28 1997-01-29 Kenneth T. Armstrong Topical phenylephrine preparation
US6294517B1 (en) 1996-02-02 2001-09-25 Nitromed, Inc. Compositions and kits comprising alpha-adrenergic receptor antagonists and nitric oxide donors and methods of use
US5922341A (en) 1997-10-28 1999-07-13 Vivus, Incorporated Local administration of pharmacologically active agents to treat premature ejaculation
US6747008B1 (en) * 2000-06-19 2004-06-08 University Of Southern California Methods for treating and preventing alopecia
US20040198706A1 (en) 2003-03-11 2004-10-07 Carrara Dario Norberto R. Methods and formulations for transdermal or transmucosal application of active agents
GB0225908D0 (en) 2002-11-06 2002-12-11 Pfizer Ltd Treatment of female sexual dysfunction
US20140011774A1 (en) * 2002-12-05 2014-01-09 University Of Tennessee Research Foundation Selective androgen receptor modulators
US6938624B2 (en) 2003-01-30 2005-09-06 Hairlocs, Inc. Methods and devices for applying hair extensions
US20060252734A1 (en) 2004-09-08 2006-11-09 Woodward John R Methods of female sexual enhancement
EP1807087A2 (de) 2004-10-12 2007-07-18 Ernir Snorrason Inhibitoren von acetylcholinesterase zur behandlung von hauterkrankungen
US20060110415A1 (en) 2004-11-22 2006-05-25 Bioderm Research Topical Delivery System for Cosmetic and Pharmaceutical Agents
HUE054887T2 (hu) 2005-06-17 2021-10-28 Wisconsin Alumni Res Found Topikális érösszehúzó készítmények és eljárások sejtek védelmére rák kemoterápia és radioterápia alatt
US7533676B2 (en) * 2005-07-11 2009-05-19 Aderans Holdings Co., Ltd. Do-it yourself removable/reusable non-chemical highlights and hair extensions
EP1790343A1 (de) 2005-11-11 2007-05-30 Emotional Brain B.V. Pharmazeutische Zusammensetzungen und deren Verwendung zur Behandlung sexueller Störungen der Frau
US20090068287A1 (en) 2007-09-12 2009-03-12 Susan Welsh Novel topical formulations of flucytosine and uses thereof
BRPI0819075A2 (pt) * 2007-11-16 2014-10-07 Vicept Therapeutics Inc Método para tratar púrpura em um indivíduo e método para diminuir a púrpura em um indivíduo antes de um procedimento cirúrgico
CN102573848A (zh) 2009-04-24 2012-07-11 济州大学校产学协力团 含有去甲加兰他敏化合物作为活性成分的用于预防和治疗脱发症的组合物
US9084891B2 (en) 2012-02-06 2015-07-21 David Aberizk Pilomotor effect stimulating device and method
JP2016047806A (ja) * 2014-08-28 2016-04-07 一丸ファルコス株式会社 フェニルエチルアミン誘導体又はシネフリン含有アデノシン三リン酸フォスファターゼ発現誘導剤
KR102476626B1 (ko) 2014-11-14 2022-12-09 폴리 인터내셔널 탈모증을 예방하기 위한 시스템 및 방법
US10064816B2 (en) 2015-06-11 2018-09-04 ReJoy Treatment of sexual dysfunction

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

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